Human cytomegalovirus protects endothelial cells from apoptosis induced by growth factor withdrawal

Schroeder, Marcella Billstrom; Christensen, Robert D.; Worthen, G. Scott

doi:10.1016/s1386-6532(02)00090-2

Cited by 20 publications

(4 citation statements)

References 14 publications

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“…The BH3‐only proteins cannot cause cell death in the absence of Bax and Bak, and hence must function upstream in the same pathway. As shown recently, HCMV infection inhibited apoptosis induced by growth factor withdrawal in primary endothelial cell cultures [116]. The cellular levels of Bcl‐xL were elevated in the HCMV‐infected cultures, thereby suggesting that HCMV infection might upregulate expression of this anti‐apoptotic protein.…”

Section: Oncomodulation and Apoptosissupporting

confidence: 59%

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression

et al. 2004

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A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested "hit and run" transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell lines - a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.

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Section: Oncomodulation and Apoptosissupporting

confidence: 59%

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression

et al. 2004

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“…Although encoding viral homologues of prosurvival Bcl‐2 proteins is commonly used to achieve this aim, the CMV seem to have developed alternative methods for interfering with apoptosis. Increased expression of the cellular prosurvival proteins Bcl‐2, Bcl‐xL or Bfl‐1/A1 has been observed in cells infected with either HCMV or MCMV 60 , 61 , 62 , 63 . Overexpression of Bcl‐2, or its prosurvival counterparts, is a well established means of preventing apoptosis 4 , 6 .…”

Section: Viral Interference With the Activities Of Bcl‐2 Family Proteinsmentioning

confidence: 99%

Insights into the mechanisms of CMV‐mediated interference with cellular apoptosis

Andoniou

Degli-Esposti

2006

Immunol Cell Biol

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Summary Apoptosis has the potential to function as a defence mechanism during viral infection. Identification of CMV mutants that cause the apoptotic death of infected cells confirmed that viral infection activates apoptotic pathways and that this process is counteracted by CMV to ensure efficient viral replication. The recent identification of CMV-encoded proteins that suppress cell death has greatly enhanced our understanding of the mechanisms used by this family of viruses to prevent apoptosis. CMV do not encode homologues of known death-suppressing proteins, suggesting that the CMV family has evolved novel, more sophisticated strategies for the inhibition of apoptosis. The identification and characterization of the human CMV (HCMV)-encoded antiapoptotic proteins UL36 (viral inhibitor of caspase-8 activation [vICA]) and UL37 (viral mitochondria-localized inhibitor of apoptosis [vMIA]) have confirmed that CMV target unique apoptotic control points. For example, vMIA inhibits apoptosis by binding Bax and sequestering it at the mitochondrial membrane as an inactive oligomer. This knowledge not only provides a more complete understanding of the CMV replication process but also allows the identification of previously unrecognized apoptotic checkpoints. Because HCMV is an important cause of birth defects and an increasingly important opportunistic pathogen, a firm grasp of the mechanisms by which it affects cellular apoptosis may provide avenues for the design of improved therapeutic strategies. Here, we review the recent progress made in understanding the role of CMV-encoded proteins in the inhibition of apoptosis.

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“…ECs exposed to these antibodies increase expression and release of HSP60 which can go on to stimulate TLR4 and lead to proinflammatory sequelae in circulation and in the vasculature [142]. It must be noted that US28 itself, not the antibodies directed against it, acts in an anti-apoptotic manner [143]. Importantly, HMCV-infected ECs express US28 on their cell membranes [143].…”

Section: Latent Infection By Herpesviruses Is Sufficient To Bring Abo...mentioning

confidence: 99%

“…It must be noted that US28 itself, not the antibodies directed against it, acts in an anti-apoptotic manner [143]. Importantly, HMCV-infected ECs express US28 on their cell membranes [143].…”

Section: Latent Infection By Herpesviruses Is Sufficient To Bring Abo...mentioning

confidence: 99%

Herpesvirus Infection as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Nunes,

Kell,

Pretorius

2024

Preprint

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Understanding the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that herpesviruses' infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment – symptoms consistent with ME/CFS and Long COVID. The paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within ECs of ME/CFS patients. This review offers a conceptual advance by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research towards potentially unexplored avenues in understanding and treating this complex syndrome.

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Human cytomegalovirus protects endothelial cells from apoptosis induced by growth factor withdrawal

Cited by 20 publications

References 14 publications

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression

Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression

Insights into the mechanisms of CMV‐mediated interference with cellular apoptosis

Herpesvirus Infection as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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